Abstract
Animals use gustatory information to decide whether to ingest nutritious substances or avoid toxic ones. Although certain neurons in the gustatory circuits respond to both aversive and appetitive signals, how these neurons resolve inputs with opposing valences is unknown. Here, we examine how the Drosophila melanogaster neuropeptide leucokinin (LK) affects gustatory information processing to elicit the appropriate feeding behaviors. We identify the subesophageal LK neurons (SELKs) as downstream synaptic partners of gustatory receptor neurons and show that these two groups are functionally connected. We then show that SELKs affect bitter avoidance through LK release and food intake in an acetylcholine-dependent manner. Our study uncovers a mechanism whereby strong activation of SELKs results in LK release, leading to feeding suppression, while weak activation results in acetylcholine-dependent feeding promotion. Thus, our results reveal that a single pair of neurons, SELKs, differentially controls opposing feeding behaviors via distinct neurotransmitters.
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Data availability
The behavioral and functional imaging data generated in this study have been deposited in the Figshare database under accession code https://doi.org/10.6084/m9.figshare.31049989. Source data are provided as a Source data file. Source data are provided with this paper.
Code availability
Custom codes used for data analyses are available at: https://github.com/Zandawala-lab/Savas-et-al-2025-Drosophila-SELK.
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Acknowledgements
This work was supported by NIH grant R01DC020703 (G.B.), Brown University Carney Institute for Brain Science, Suna Kıraç Fund for Brain Science (D.S.), Brown University Carney Institute for Brain Science, Graduate Award in Brain Science (D.S.) and NIH/NIDCD award F31DC019540 (A.M.C.). Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. We thank Dr. Brian Kim for conducting preliminary behavioral studies. We thank Susan Brenner-Morton and Drs. Dick Nässel and Matthias Schlichting for sharing reagents. We would like to thank Drs. Karla Kaun, Alexander Fleischmann, Mustafa Talay, and members of the Barnea Laboratory for critical reading of the manuscript.
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D.S., M.Z., and G.B. conceptualized the study. D.S., A.O., R.A.M., A.M.C., Z.C., R.S., A.S., and M.Z. contributed to the acquisition and analysis of the data. D.S. and G.B. administered the project. D.S. and G.B. wrote the manuscript. The project was supervised by M.Z. and G.B.
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Savaş, D., Okoro, A.M., Moșneanu, R.A. et al. Feeding decision-making by a single neuron via disparate neurotransmitters. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69443-8
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DOI: https://doi.org/10.1038/s41467-026-69443-8
